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???displayArticle.abstract??? Thyroid hormone controls remodeling of the tadpoleintestine during the climax of amphibian metamorphosis. In 8 days, the Xenopus laevis tadpoleintestine shortens in length by 75%. Simultaneously, the longitudinal muscle fibers contract by about the same extent. The radial muscle fibers also shorten as the diameter narrows. Many radial fibers undergo programmed cell death. We conclude that muscle remodeling and contraction play key roles in the shortening process. Shortening is accompanied by a temporary "heaping" of the epithelial cells into many layers at climax. Cells that face the lumen undergo apoptosis. By the end of metamorphosis, when the epithelium is folded into crypts and villi, the epithelium is a single-cell layer once again. Throughout this remodeling, DNA replication occurs uniformly throughout the epithelium, as do changes in gene expression. The larval epithelial cells as a whole, rather than a subpopulation of stem cells, are the progenitors of the adult epithelial cells.
Fig. 1. The tadpolegut shortens dramatically during metamorphosis. The components of the gut depicted here are as follows: es, esophagus; st, stomach; du, duodenum; il, ileum; co, colon; re, rectum. The duodenum and part of the ileum comprise the intestine's outer loops that coil in a counterclockwise direction (ventral perspective). The ileum reverses direction at the switchback point (arrowhead) and coils clockwise with the colon to form the intestine's inner loops. The rectum is the final internal structure of the gut. (A) The gut of a premetamorphic NF 54 tadpole (Inset) is shown both in situ (upper) and excised and uncoiled (lower). (B) A prometamorphic NF 58 tadpole (Inset) has a much larger and longer gut than an NF 54 tadpole. (C) In a tadpole at metamorphic (NF 62) climax (Inset), the length of the gut has begun to shorten, and the number of outer and inner coils has decreased. (D) By the end of metamorphosis (NF 66) (Inset), the gut has shortened by ≈75% of its original length. (Scale bars: 2 mm.)
Fig. 2. The intestinal epithelium thickens during metamorphic climax. Cross sections of the duodenum at different developmental stages are labeled with antibodies against proteins that are localized in the epithelium (e-cadherin, green) and mesenchyme (fibronectin, red). Nuclei are labeled with DAPI (white). (A and A′) Before metamorphosis (NF 54), the epithelium is only one to two cell layers thick. During metamorphic climax (B and B′,NF62; C and C′, NF 63), the epithelial layer becomes five to eight cell layers thick. (D and D′)At the end of climax (NF 66), the epithelium returns to one to two cell layers thick. [Scale bars: 100 μm (A–D) and 20 μm (A′–D′).] The boxed regions in A–D correspond with the magnified regions shown in A′–D′.
Fig. 3. Three different developmental profiles of gene expression in the intestinal epithelium. Cross sections of the tadpoleduodenum are shown at the following stages. (A–C) Premetamorphosis, NF 54. (A′–C′) Metamorphic climax, NF 62. (A′–C′) Postmetamorphosis, NF 66. Sections on slides were hybridized with antisense mRNA probes. (A–A′) Musashi is expressed constitutively in the epithelium before, during, and after metamorphosis. (B–B′) Intestinal fatty acid binding protein is expressed in the epithelium before metamorphosis, and the expression eclipses during climax and returns at the end of metamorphosis. (C–C′) Basic leucine zipper expression is absent before climax, is up-regulated in both the epithelium and mesenchyme during climax, and is down-regulated at the end of climax. (Scale bar:100 μm.)
Fig. 4. Cell proliferation in the intestinal epithelium during tadpole metamorphosis. Proliferating cell nuclei were labeled with a 12-h pulse of BrdUrd injected i.p. into living tadpoles. Cryosections of the duodenum were stained with antibodies against BrdUrd (e-cadherin, green) and mesenchyme (fibronectin, red). (A) BrdUrd label is very low during premetamorphosis (NF 54); increases uniformly throughout the epithelium during metamorphic climax at stages NF 60 (B), NF 61 (C), and NF 62 (D); and continues to be widespread near the end of climax at NF 65 (E). (F) By the end of climax (NF 66), BrdUrd incorporation begins to decrease at the crest regions of the intestinal involutions. (G) Localization of BrdUrd incorporation to cells in the troughs is apparent 2 weeks after completion of metamorphosis. (Scale bar: 100 μm.)
Fig. 5. Active caspase-3 immunoreactivity in the tadpoleintestine varies with developmental stage. Intestines (duodenum) at different stages of metamorphosis were labeled in cryosections (A–C) with antibodies against active caspase-3 (green), smooth muscle (red), and nuclei counterstained with DAPI (white). (A) NF 58 tadpole. (B) Climax at NF 61. (C) The end of climax (NF 66). (Scale bar: 100 μm.)
Fig. 6. Intestinal smooth muscle fibers shorten in response to TH treatment. Intestines were excised at 0 h (A and C) and 72 h (B and D) after treatment with 10 nM T3 and labeled in whole-mount by using antibodies against either smooth muscle actin (A and B) or e-cadherin (C and D). Longitudinal muscle fibers are oriented horizontally, and radial fibers are oriented vertically. [Scale bars: 20 μm (A and B) and 500 μm (C and D).]
cdh1 (cadherin 1, type 1, E-cadherin (epithelial)) gene expression (green) in cross-section of Xenopus laevis gut, NF stage 66, as assayed by immunohistochemistry.
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